Translation initiation events on structured eukaryotic mRNAs generate gene expression noise.
Translation initiation events on structured eukaryotic mRNAs generate gene expression noise.
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DOI：
10.1093/nar/gkx430
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发表时间：
2017-06-20
影响因子：
14.9
通讯作者：
McCarthy JEG
中科院分区：
文献类型：
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作者：
Dacheux E;Malys N;Meng X;Ramachandran V;Mendes P;McCarthy JEG
基因表达的随机性在生物学中发挥着重要作用，它创造了非遗传的细胞个性，并影响了包括分化和应激反应在内的多个过程。我们已经解决了缺乏关于转录后对噪声的贡献的知识，通过确定酵母中mRNA和报告蛋白丰度的细胞到细胞的变化。两种类型的结构元件，茎环和Poly(G)基序，当插入到mRNA5΄非翻译区时，不仅抑制翻译起始，而且还产生噪声。当与上游开放阅读框架结合时，茎环结构的噪音增强效果也仍然有效。这具有广泛的意义，因为已知这些元件可以调节多种真核基因的表达。我们的发现提出了一种转录后噪声产生的机制，这将有助于理解蛋白质水平的随机性和转录爆发之间通常较差的相关性。我们认为转录后的随机性可以与茎环结构的折叠/展开周期有关，也可以与富含G的基序的高阶结构构象之间的相互转换有关，并建立了一个相应的配置计算模型，该模型产生了与实验数据相匹配的结果。因此，核糖体扫描过程中发生的随机事件可以与转录猝发一起作为噪声源。
Gene expression stochasticity plays a major role in biology, creating non-genetic cellular individuality and influencing multiple processes, including differentiation and stress responses. We have addressed the lack of knowledge about posttranscriptional contributions to noise by determining cell-to-cell variations in the abundance of mRNA and reporter protein in yeast. Two types of structural element, a stem–loop and a poly(G) motif, not only inhibit translation initiation when inserted into an mRNA 5΄ untranslated region, but also generate noise. The noise-enhancing effect of the stem–loop structure also remains operational when combined with an upstream open reading frame. This has broad significance, since these elements are known to modulate the expression of a diversity of eukaryotic genes. Our findings suggest a mechanism for posttranscriptional noise generation that will contribute to understanding of the generally poor correlation between protein-level stochasticity and transcriptional bursting. We propose that posttranscriptional stochasticity can be linked to cycles of folding/unfolding of a stem–loop structure, or to interconversion between higher-order structural conformations of a G-rich motif, and have created a correspondingly configured computational model that generates fits to the experimental data. Stochastic events occurring during the ribosomal scanning process can therefore feature alongside transcriptional bursting as a source of noise.